1. Field of the Invention
The invention is in the general field of nutrients, dietary supplements, and metabolic regulators
2. Description of the Related Art
One of the few methods known to consistently produce prolongation of lifespan across multiple species is caloric restriction. Caloric restriction involves practicing a generally balanced diet, while restricting caloric intake levels to about 25-30% below the levels that an organism might normally consume. The impact of caloric restriction on short lived mammals, such as rodents, is impressive, with a near doubling of lifespan being reported. Studies of caloric restriction in primates, such as rhesus macaques, although still ongoing, have also demonstrated reduced death rates, as well as a marked decrease in age related conditions such as lower rates of cancer, diabetes, and heart disease. In humans, caloric restriction has been demonstrated to improve memory, as well as lower blood pressure, cholesterol, and triglycerides.
Despite these promising findings, caloric restriction is extremely difficult to follow, because individuals practicing caloric restriction are hungry essentially all of the time. Caloric restriction practitioners also suffer from increased sensitivity to cold, lower muscle mass, and may also be more prone to bone disorders. Thus there is a high level of interest in finding ways to produce the beneficial effects of caloric restriction through other means.
It is been known for many years that nutrients such as glucose and non fiber carbohydrates mediate many of their detrimental effects on the body through the activity of insulin, and indeed the problems caused by excess carbohydrates and excess insulin are well documented. Recently, studies have demonstrated that other nutrients, such as dietary amino acids have profound effects upon a recently discovered mTOR metabolic pathway, and the mTOR pathway in turn regulates many other metabolic pathways producing effects that are closely associated with the same effects obtained with caloric restriction. Indeed it has been postulated that the beneficial effects of caloric restriction may be secondary to regulatory effects of the mTOR pathway on an evolutionarily conserved genetic expression of maintenance and repair mechanisms resulting in the phenotype of longevity.
mTOR, which stands for the mammalian target of rapamycin, is a cell protein that has been found to regulate cell growth, proliferation, motility, and survival, as well as protein synthesis and protein transcription. mTOR essentially acts to integrate signals from multiple sources, including amino acids and insulin, and in turn pass these signals along to other regulatory proteins in the mTOR signaling pathway. mTOR is inhibited by the drug rapamycin, which interestingly has been shown to inhibit cancer and increase lifespan in rodents. As a result, there is much interest and speculation at present that the beneficial effects of caloric restriction may be mediated through the mTOR pathway, and further that finding alternate and safe ways to inhibit the mTOR pathway may have beneficial and possibly lifespan enhancing effects.
Although mTOR is stimulated by amino acids, studies have shown that not all amino acids stimulate mTOR equally. Rather, studies have consistently shown that one amino acid in particular, leucine, is by far the most potent stimulator of the mTOR pathway. Other work has suggested that another amino acid, methionine, may also be important, either through the mTOR pathway or through an analogous but as of yet poorly characterized alternate pathway.
Prior publications in this field include:    Counting the Calories: The Role of Specific Nutrients in Extension of Life Span by Food Restriction Matthew D. W. Piper, William Mair, and Linda Partridge, Gerontological Society of America 2005, Vol. 60A (5) 549-555.    Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Aging Cell. 2006 August; 5(4):305-14. Epub 2006 Jun. 26.    The amino acid sensitive TOR pathway from yeast to mammals Stephen G. Dann, George Thomas FEBS Letters 580 (2006) 2821-2829. This publication gives a good overview of the mTOR (target of rapamycin TOR pathway) and discusses how this pathway is an evolutionary preserved cell growth sensor of signals from growth factors and nutrients, particularly amino acids such as leucine.